AND THE NOMINEES ARE:
Despite their incredibly small size, nanoparticles have already been identified to serve in a diverse range of applications, with further uses continually being investigated. One of the most heavily researched applications of nanoparticles is their potential use in targeted pharmaceuticals. For example, the small size of gold nanoparticles allows them to penetrate through porous vasculature at specific sites within the body, such that they can selectively accumulate within that site. If we coat nanoparticles with certain drug molecules, we can potentially target that drug to the area of interest rather than allowing it to concentrate in other locations throughout the body where it can produce harmful side effects.
New cancer research is exploring the attachment of chemotherapeutic drugs to the surface of gold nanoparticles in order to apply EPR to selectively target the drugs to the tumor site.
Despite being very small and sounding very complicated, [some types of] gold nanoparticles are relatively simple to synthesize in large volumes. This is important when producing large quantities of nanoparticles for industrial applications.
A little bit of citrate into a little bit of gold gives us a big batch of bright red gold nanoparticles! (Yes…gold nanoparticles are red, not gold)
This brings us to my current work. We are currently exploring the potential of using gold nanoparticles as carriers for antidepressants, specifically the Selective Serotonin Reuptake Inhibitor (SSRI) fluoxetine (Prozac ®).
We have been examining two methods by which we can prepare a fluoxetine-loaded polymer that can attach to the surface of our gold nanoparticles. Most nanoparticles cannot exist on their own; they need some type of molecular coating – a surfactant – to provide stability. In the nanoparticles with which I am working, negatively charged citrate provides charge screening against other negatively charged particles. While it is possible to attach molecules individually to the nanoparticle, it would involve replacing the citrate stabilizer with the drug, thus reducing the charge stability of these particles, causing them to aggregate (which is BAD!) Therefore, we are exploring methods to incorporate fluoxetine into a polymer that we attach to the gold nanoparticle. The polymer acts as a coating to prevent the particles from colliding with each other (which is GOOD!)
Just because we work in an analytical chemistry lab, it doesn’t mean we can’t do some synthetic organic chemistry too!
Mix some polymer with some nanoparticles à get some polymer coated nanoparticles.
As nanotechnology is a relatively new concept in the context of pharmaceutical delivery, a substantial amount of work is being performed in order to quantify the amount of drug molecules attached to each nanoparticle. Unfortunately, we can’t simply grab a nanoparticle and count the number of drug molecules, so we have to employ some other methods. Now that we have synthesized our fluoxetine-linked gold nanoparticles, the bulk of our work involves quantifying the amount of fluoxetine per nanoparticle. One of these methods involves the bromination of fluoxetine and methyl orange dye to perform spectrophotometric measurements.
When there is more fluoxetine, more Br2 is consumed; therefore there is less Br2 available to inactivate methyl orange, such that the reaction will have a greater absorption of light.
One of the concerns about nanomaterials and many pharmaceuticals is their persistence in the aquatic environment once released via wastewater. For this reason, we plan to assess our fluoxetine-nanoparticle conjugates on a variety of aquatic model organisms, such as frog tadpoles.
I am new to the lab this summer, so I’m looking to build off a previous lab member’s project. Celina’s work looked to quantify the number of polymers, specifically polystyrene sulfonate (PSS) that were wrapping around each gold nanoparticle. The work that she did involved developing and optimizing a dialysis stage to “clean” the nanoparticles in order to remove any excess polymers in solution. Over the course of these eight weeks, my project, while still in it’s initial stages, will look to explore the effects of changing the identity of the salt during the coating stage.
I have looked at how changing between the salts lithium, potassium and sodium chloride respectively changes either the “thickness” of the polymer coating or even the number of polymers associated with the nanoparticles. The first trial has just been completed and the data is currently being processed! The results suggest that there is a difference in the number of polymers per nanoparticle, but more trials will have to be conducted in order to determine whether this is statistically significant.
Some of the difficulties that I have run in to are both the pace of the dialysis and the difficulties associated with making large batches of monodisperse particles. The dialysis process, while efficient, lasts up to a full day meaning that it’s roughly a week-long window in order for one trial of results to be collected. This means that any alterations to the procedure take a while to be observed. The monodisperse particles, however, are more important. Given that analytical techniques are being used to calculate the number of polymers per gold nanoparticle, the surface area and thus the size of the nanoparticles are important to control. During the first couple of weeks in this lab therefore, I worked on refining the production of 250 mL batches of spherical nanoparticles.
Two weeks ago, the lab also attended the regional ACS Conference in Hershey, PA. Even though the day started at 6.30 (yes A.M) I thoroughly enjoyed my first Chemistry conference. The days were divided into several different larger topics, but some of my favourite talks that I attended were a guide to a chemical history walking tour in Paris and another talk about the future of 3D printed personalized medication!
This summer I am continuing my work on polyelectrolyte quantification on the surface of gold nanoparticles. I am additionally studying the thermodynamics of the binding interactions between polyelectrolytes and gold nanoparticles using an instrument called the Isothermal Titration Calorimeter. The isothermal titration calorimeter, or ITC for short, is a way of carrying out small-scale titrations to determine key thermodynamic properties such as binding constants, enthalpy, and the stoichiometry of a reaction. In other words, it is basically a very expensive thermometer. The ITC works by injecting a very small amount of a specific polyelectrolyte over time into the sample cell, which contains the gold nanoparticles. The instrument measures the heat that is absorbed or released for each injection. At the moment, I am working on testing different concentrations of polymer to see which concentrations cause the nanoparticles to aggregate, or deform, before the solutions are used in the ITC. Once the optimal concentrations are found, I will be able to use those solutions to measure the binding interactions.
My other project looks at the quantification of polyelectrolytes on the surface of gold nanoparticles. We begin by synthesizing the nanoparticles via a seed-mediated growth method. The nanoparticles are then coated with a polymer, polyanetholesulfonic acid, also known as PAS. Last summer we did the same procedure with a different polymer, polystyrene sulfonate (PSS). We decided to use PAS due to its similarities in molecular structure to PAS. Ultimately we are testing to see if a polyelectrolyte with a smaller molecular weight, such as PAS, will vary in the quantification of polyelectrolyte on the surface of the nanoparticles compared to polyelectrolytes with a larger molecular weight, such as PSS. The coated nanoparticles must undergo a vigorous purification process to make sure the excess polymer is removed and we can quantify the polymer that is tightly bound to the surface of the nanoparticles. I am currently working on optimizing the purification process for PAS coated nanoparticles, as the particles are more prone to aggregation due to the smaller mass of the polymer.
After undergoing the purification, the particles are analyzed using Inductively-Coupled Plasmon Optical Emissions Spectroscopy, or ICP-OES. The particles are passed through the instrument where they are exposed to a plasma flame that is about the temperature of the surface of the sun, or around 15,000 degrees Fahrenheit! The hot plasma breaks all of the bonds in the solution, exciting the electrons. The ICP-OES measures the intensity of the light that is given off as the electrons return to their respective ground state. We are ultimately able to determine the number of polymer units per gold nanoparticle by the concentrations that the instrument works out from the intensities. This involves many Excel spreadsheets and a lot of patience!
When I’m not in the lab, I have spent most of my time supporting the best hockey team on the planet, the Pittsburgh Penguins, as they won the Stanley Cup for the second year in a row! LGP!
AND THE WINNER IS: